To investigate how human liver cells prevent or retard the malignant effects of chronic exposure to carcinogens present in the environment, the enzymology of the excision repair of DNA damaged by model environmental carcinogens will be investigated. In these initial studies a key DNA repair enzyme, human liver DNA endonuclease specific for apurinic/apyrimidinic sites (apurinic DNAse), will be studied. Preliminary studies have demonstrated that autopsy liver is a rich source of apurinic DNAse and have also suggested that the activity of apurinic DNAse in autopsy livers is fairly stable. In initial experiments, phosphocellulose chromotography has revealed multiple species of human liver apurinic DNAse. Each species of apurinic DNAse will be purified further by column chromotography on DNA cellulose and hydroxyapatite. The specificity of endonucleolytic incision by each enzyme will be examined by assaying incision with apurinic DNA, with apyrimidinic DNA, and with DNA damaged methyl methane sulfonate, by nitrogen mustard, by N-acetoxy-2-acetylaminofluorene, and by ultraviolet irradiation. Each purified apurinic DNAse will be tested for associated non-endonucleolytic activities including DNA exonuclease, DNA phosphatase, and DNA glycosidase. Taken together these studies should begin to define how human liver cells repair DNA damaged by environmental carcinogens.